• During the beginning of the COVID-19 outbreak in the United States, the WHO said people shouldn’t take ibuprofen if they had COVID-19.
• A new report found that nonsteroidal anti-inflammatory drugs like ibuprofen aren’t linked to any adverse effects in people who were positive for SARS-CoV-2, the coronavirus that causes COVID-19.
• COVID-19 is a multi-system disease that can seriously affect the kidneys, gastrointestinal tract, and heart, along with many other organs.

During the beginning of the COVID-19 outbreak in the United States, the World Health Organization (WHO) said that people shouldn’t take ibuprofen if they had COVID-19.

The organization then backtracked and said they didn’t recommend against it. Now, newly published research shows that the medication isn’t associated with having more severe disease.

Ibuprofen belongs to a class of medications known as nonsteroidal anti-inflammatory drugs (NSAIDs).

The WHO’s response was based on a report out of France published in March that drew concerns about ibuprofen making COVID-19 symptoms worse.

Now, a new report published Sept. 8 in PLOS Medicine found that NSAIDs aren’t linked to any adverse effects in people who were positive for SARS-CoV-2, the virus that causes COVID-19.

For the study, researchers assessed data on all 9,236 Danish residents who tested positive for SARS-CoV-2 between Feb. 27 and April 29, 2020. Of them, 248 people (or 2.7 percent) filled a prescription for NSAIDs within 30 days of their positive COVID-19 test.

Of those who tested positive and used NSAIDs:

• 6.3% died
• 24.5% were hospitalized
• 4.9% were admitted to the hospital’s intensive care unit (ICU)

Of those who tested positive and didn’t use NSAIDs:

• 6.1% died
• 21.2% were hospitalized
• 4.7% went to the ICU

None of the data from the groups were statistically significant.

“Considering the available evidence, there is no reason to withdraw well-indicated use of NSAIDs during the SARS-CoV-2 pandemic,” the authors state. There are well-established adverse effects from NSAIDs, which should be considered in any patient.

“I would urge caution to jumping to any conclusions,” Dr. Joseph Poterucha, an ICU physician with the Mayo Clinic Health System in Wisconsin, told Healthline.

That’s because there are numerous side effects of NSAIDs, including cardiac, renal, and gastrointestinal complications that need to be considered, he added.

“In certain individuals with chronic medical comorbidities, the burden of this side effect profile in concert with an active coronavirus infection could be detrimental,” he said.

In other words, people with chronic kidney disease, heart failure, history of stroke, and history of stomach ulcers complicated by gastrointestinal bleeding should avoid NSAIDs in general.

Unknowns about possible ACE2 connection

Early research claimed that SARS-CoV-2 binded to target cells via angiotensin-converting enzyme 2 (ACE2).

Patients likely have increased ACE2 expression if they’re treated with ACE inhibitors, angiotensin II type I receptor blockers (ARBs), or thiazolidinediones, according to an April study in The Lancet.

Authors of that study were concerned that people taking drugs that could increase ACE2 (such as those with cardiovascular disease, hypertension, and diabetes) could have more serious COVID-19, especially if those people also took ibuprofen and that also increased ACE2 levels. That was the initial hypothesis that drew concerns globally, along with the BMJ report.

“This association with ACE2 up regulation in NSAIDs has not been well delineated in the medical literature,” Poterucha said. “More study is needed.”

As such, patients should always talk to their doctors about taking NSAIDs, especially if they have heart, kidney, cerebrovascular, and gastrointestinal disease.

“The fact that ibuprofen boosts ACE2 is derived from rat studies, and this effect may not necessarily crossover to humans,” noted Dr. Gurusaravanan Kutti-Sridharan, a clinical associate professor at Banner University Medical Center at the University of Arizona.

The concerns that people taking ibuprofen could be more susceptible to worse COVID-19 were legitimate. But we don’t know if ibuprofen raises ACE2 levels in humans, and if so, to what extent it may boost susceptibility to COVID-19, Kutti-Sridharan told Healthline.

Anton Pottegård, PhD, an author, pharmacoepidemiologist, and clinical pharmacist at the University of Southern Denmark and colleagues, said he would like to see more research to replicate his findings.

“However, considering the fairly hypothetical grounds on which the initial concern was raised, I would argue that we at the present time have limited reason to provide specific guidance for ibuprofen use specifically in relation to COVID-19,” Pottegård told Healthline.

Is ibuprofen okay in people with COVID-19?

Because this is a cohort study, its design could be vulnerable to biases including sampling, ascertainment, and observer bias. The gold standard is usually a randomized control trial, Poterucha said.

“Much more study is needed to definitively understand adverse effects of NSAIDs and morbidity of COVID-19 ahead,” Poterucha said.

There were more than 9,000 people to draw data from in this study, along with a matched cohort, so the research does show valuable information, said Dr. Rodney E. Rohde, an associate dean for research at Texas State University’s College of Health Professions focusing on public health microbiology.

“However, I would continue to want to see more, larger studies looking across a strong sampling of demographics of populations before drawing any final conclusions,” he told Healthline.

“There is not sufficient evidence to recommend those who take ibuprofen for other indications to stop or change ibuprofen to a different anti-inflammatory medication because of the COVID-19 pandemic,” Kutti-Sridharan said.

That said, it doesn’t mean that it’s entirely safe to take ibuprofen over the counter to manage fever or pain due to COVID-19.

COVID-19 isn’t just a respiratory illness but a multi-system disease that can seriously affect the kidneys, gastrointestinal tract, and heart, along with many other organs.

“Given its potential for renal, gastrointestinal, and cardiovascular side effects, ibuprofen use, if indicated, should be restricted to the lowest effective dose for the shortest possible period, preferably under a doctor’s guidance to avoid serious adverse outcomes,” he added.

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